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Review Black Walnuts (Juglans nigra L.): Potential as a Health Promoting Food Cristiane Rodrigues Silva Câmara, M.Sc. a and Vicki Schlegel, Ph.D. a,* a Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, USA * Corresponding author. Tel.: +1-402-416-0294. E-mail address: [email protected]. - Word count (including tables and figures ): 5046 words - Number of tables: 1 - Number of figures: 1

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Page 1: Black Walnuts (Juglans nigra L.): Potential as a Health ...Walnuts, almonds and pecans are the top three nuts consumed in the United States (USDA/ERS, 2012a). Walnut is the second

Review

Black Walnuts (Juglans nigra L.): Potential as a Health

Promoting Food

Cristiane Rodrigues Silva Câmara, M.Sc. a and Vicki Schlegel, Ph.D.

a,*

a Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln,

USA

* Corresponding author. Tel.: +1-402-416-0294.

E-mail address: [email protected].

- Word count (including tables and figures ): 5046 words

- Number of tables: 1

- Number of figures: 1

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2

Abstract: Nut consumption has been reported to protect against cardiovascular

disease, certain types of cancer, diabetes and others disease states, including

neurodegenerative conditions. The nutrient composition of black walnuts

indicates that this edible nut has a strong potential on human health promoting.

However, scientific studies on the functional properties of black walnut are

extremely scarce. Thus, the aim of this review was to evaluate the potential black

walnuts consumption on human-health promotion, using recent evidences

obtained from English walnuts research, as both classes have comparable

bioactive compounds composition. Compared to English walnut, the most

marketed and studied walnut, and other classes of nuts, black walnut contains

higher content of polyunsaturated fatty acids levels and antioxidants agents, such

as polyphenolic compounds and γ-tocopherol, which has been extensively

correlated with prevention and/or attenuation of those cited diseases. Moreover,

other nutrients present in black walnuts are linked with those benefic effects, ,

including dietary fiber, folate, phytosterols, vegetable protein, melatonin, among

others. The information provided herein provide strong evidence that black

walnuts can be readily incorporated into diet as a means to produce multiple

beneficial health outcomes.

Keywords: Black walnut; English walnuts; health benefits; PUFAs; antioxidants

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1. Introduction

Several epidemiologic and clinical studies have reported remarkable health benefits

through the consumption of tree nuts, including effects against cardiovascular diseases

(CVDs), diabetes, inflammatory process, oxidative stress, cancer and neurodegenerative

conditions (Djoussé et al., 2008; Gonzalez et al., 2006; Hu et al., 1998; Damasceno et al.,

2011; Carvalho et al. 2010; Poulose et al. 2012; Pan et al. 2013; Pereira et al., 2007, Willis et

al., 2010). The health promoting properties derived from these plant sources have been

mainly attributed to their unsaturated fatty acids composition and other bioactive nutrients

such as phenolic compounds, tocopherols, phytosterols, high-quality vegetable protein, fiber

and minerals (Ros and Mataix, 2006; Brufau et al 2006 ; Segura et al. 2006; Oliveira et al.,

2008).

Tree nuts are dry fruits with one seed in which the ovary wall becomes hard at

maturity. The most popular edible nuts are almonds (Prunus amigdalis), hazelnuts (Corylus

avellana), walnuts (Juglans regia), pistachios (Pistachia vera), pine nuts (Pinus pinea),

cashews (Anacardium occidentale), pecans (Carya illinoiensis), macadamias (Macadamia

integrifolia), and Brazil nuts (Bertholletia excelsa) (Ros, 2010).

Walnuts, almonds and pecans are the top three nuts consumed in the United States

(USDA/ERS, 2012a). Walnut is the second most produced, with 504,000 tons produced in

2010 (USDA/ERS, 2012b) and standing behind of only almonds (820,000 tons) (USDA/ERS,

2012c). California is the largest producer and processor of 90% of nuts with far exceeding

other states (USDA/ERS, 2012a).

The two most produced varieties of walnuts in the U.S. are the English walnuts or

common walnut (Juglans regia L.) and the Black walnus (Juglans nigra L.). English walnuts,

the most commercially cultivated, originated in Persian and expanded to U.S. through English

settlers. The Black walnut is native to the Midwest and Northeastern United States. These

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nuts are typically harvested in Missouri from the wild when they fall from trees in forested

areas. Black walnut trees produce high-value, hardwood products and flavored edible nuts,

however, the commercial value of the latter market is because itssmall kernels andhard and

thick shells, which is difficult to hull (USDA /ERS, 2005). English and Black walnuts are

typically sold in the market as a snack or as cooking ingredient for candies, cereals, baked

goods and others sweets. Ninety percentof walnuts are sold in-shell, as most consumers

perfor to crack the nuts (AgMRC, 2007).

The majority of the published works associating walnut consumption and health

benefits are based on English walnuts studies, however similar research on Black walnuts are

extremely scarce. Thus, the aim of this review is evaluate the broad range of potential effects

of Black walnut on health promotion, taking into account its composition and similarity with

the common walnut. The comparisons reviewed herein can stimulate future research in this

field and also promote a consumption of Black walnuts by increasing our understanding on

the potential health promoting properties of these nuts.

2. Black Walnuts Composition

Black walnuts are nutrient dense foods that contain high levels of lipids, protein

(approximately 15% of energy), fiber, vitamins, minerals and also other bioactive molecules,

such as phenolic compounds and phytosterols. Table 1 shows the basic nutrient composition

relative to Black and English walnuts. As the other nuts, Black walnuts are rich dietary

sources of unsaturated fatty acids (Ros and Mataix, 2006), monounsaturated fatty acids

(MUFAs) and polyunsaturated fatty acids (PUFAs) accounting for more than 80% of the

total lipid content . MUFAs profile is comprised mainly of oleic acid (C18:1n-9) and omega-

6 linoleic acid (LA 18:3n-6); omega-3 α-linolenic

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Table 1. Black and English walnut nutrient composition (USDA/ARS, 2012).

Nutrient Unit Value per 100g*

Proximates Black walnut English walnut

Water g 4.56 4.07

Energy kcal 618 654

Protein g 24.06 15.23

Total lipid (fat) g 59.00 65.21

Carbohydrate, by difference g 9.91 13.71

Fiber, total dietary g 6.8 6.7

Sugars, total g 1.10 2.61

Minerals

Calcium, Ca mg 61 98

Iron, Fe mg 3.12 2.91

Magnesium, Mg mg 201 158

Phosphorus, P mg 513 346

Potassium, K mg 523 441

Sodium, Na mg 2 2

Zinc, Zn mg 3.37 3.09

Vitamins

Vitamin C, total ascorbic acid mg 1.7 1.3

Thiamin mg 0.057 0.341

Riboflavin mg 0.130 0.150

Niacin mg 0.470 1.125

Vitamin B-6 mg 0.583 0.537

Folate, DFE µg 31 98

Vitamin A, RAE µg 2 1

Vitamin A, IU IU 40 20

Vitamin E (alpha-tocopherol) mg 1.80 0.70

Vitamin E (gamma-tocopherol) mg 28.48 20.85

Vitamin K (phylloquinone) µg 2.7 2.7

Lipids

Fatty acids, total saturated g 3.368 6.126

Fatty acids, total monounsaturated g 15.004 8.933

Oleic acid (C18:1) g 14.533 8.7

Fatty acids, total polyunsaturated g 35.077 47.174

Linoleic acid (C18:2) g 33.072 38.2

α-linolenic acid (C18:3) g 2.006 9.08

* Nutrient values refer to edible portion.

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acid (ALA; 18:3n-3) are the major contributors for the PUFAs levels in both types of walnuts

(Table 1). Importantly, more than half of the total content of lipids is PUFAs, in Black and

English walnuts.

LA and ALA are considered essential fatty acids as they are not synthesized in the

human body and are mostly obtained from the diet (Das, 2006). Epidemiologic studies have

shown overall improvement in the health of individuals with cardiovascular heart disease

(CVD) when fed the ALA (Kris-Etherton, 2003). After absorption into a cell, LA is elongated

and desaturated to arachidonic acid (AA) while ALA is converted by a series of elongation

and desaturation reactions into eicosapentaenoic acid (EPA) and then into docosahexaenoic

acid (DHA) (Leaf et al, 2008; Harris et al., 2008; Willis et al. 2009a). Leukotrienes,

prostaglandins, and thromboxanes, metabolites derived from AA, are generally pro-

inflammatory and proaggregatory agonists, while those derived from the ALA are able to

inhibit platelet aggregation and inflammation. The latter mechanisms are involved in the

prevention of CVD, hypertension, type 2 diabetes, chronic obstructive pulmonary disease,

among others (Simopoulos, 1999). Thus, the lipid profile of Black walnuts is likely to be an

important key factor to beneficial health effects.

Walnuts are also rich sources of antioxidant vitamin E (tocopherol), with γ-tocopherol

the predominant isomer present in significant amount in Black walnuts, even more than

English walnuts (Table 1). Although γ-tocopherol has not been investigated as intensively as

α-tocopherol, recent studies have reported high antioxidant activity of this molecule and

correlated its biological function with cancer and CVDs prevention (Wagner et al., 2004).

In addition to tocopherol, walnuts are rich in phenolic compounds that increase the

antioxidant potential of this food (Blomhoff et al., 2006; Yang et al., 2009). The major

phenolic compounds frequently identified in walnuts are phenolic acids and condensed

tannins (Labuckas et al., 2008, Ito et al., 2007), including ellagic acid, ellagitannins, gallic

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acid and hydrocinnamic acids like chlorogenic acid (Anderson et al., 2001; Canales et al.,

2007). Phenolic acids are a subclass of the phenolic compounds that contain at least one

aromatic ring and one hydroxyl group in their molecule (Tsao, 2010). Condensed tannins or

proanthocyanidins are polymeric flavonoids constructed from at least two linked catechin

units (Khanbabaee and Ree, 2001). Flavonoids (e.g. catechin) are the largest subclass of

polyphenols in the human diet and are characterized by two or more aromatic rings

containing at least one hydroxyl group in each (Tsao, 2010). Figure 1 illustrates the basic

chemical structure of those cited phenolic compounds.

Phenolic compounds are mainly concentrated in the hull (the skin that covers the

kernel) and this fraction is reported to have improved human health effects (Fukuda et al.,

2003). Importantly, a review study reported that antioxidants in walnuts possess high

bioavailability (Manach et al., 2005). In an in-vitro study, the total phenolic concentration of

English walnuts was higher (550 ± 11 mg catechin equivalents per gram of tannin fraction)

than hazelnut (329 ± 7) and almonds (83 ± 2) (Karamac, 2009). Total phenolic analysis of

Black walnuts showed a concentration of 2.45 ± 0.01 mg trans-cinnamic acid equivalents per

gram of kernel (data not published), which was slightly higher in English walnuts (2.14 mg

gallic acid equivalents per gram of kernel) reported by Carvalho et al. (2010). In a different

study, Rorabaugh et al. (2011) reported that English walnuts contain a greater profile of

flavonols, a subclass of flavonoids, compared to Black walnuts. In this study, the compounds

identified in both types of walnuts were 5-caffeoylquinic acid, 4-caffeoylquinic acid,

quercetin-3- rutinoside, quercetin-3-galactoside, quercetin- 3-pentoside, quercetin-3-

arabinoside and quercetin-3-rhamnoside. Thus, the phenolic content of Black walnuts may

play an important role in the inhibition of oxidation process leading to health promotion.

Other abundant nutrients in walnuts are folate, melatonin, pectin and some minerals;

those have been associated to the improvement of lipid profile, endothelial function and

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increased plasma antioxidant capacity, and also demonstrated neuroprotective action (Tapsell

et al., 2004, Willis et al., 2009a and 2009b, Banel and Hu, 2009, Ma et al., 2010, McKay et

al., 2010, Segura et al., 2006). It must be noted that the B vitamin, folate, plays a role in

detoxifying homocysteine, a methionine derived amino acid with atherothrombotic properties

that accumulates when folate is deficient, as well as vitamin B6 and B12 (Welch and

Loscalzo, 1998). Moreover, walnuts contain high levels of arginine, 3.62 g per 100 g of

Black walnut and 2.28 g per 100 g of English walnut (USDA/ARS, 2008), which has been

linked to lowering blood pressure. This amino acid is a precursor of nitric oxide (NO), an

endogenous vasodilator (Huynh and Chin-Dusting, 2006).

Additionally, walnuts composition contain considerable non-cholesterol sterols levels

known as plant sterols or phytosterols (Segura et al., 2006). Black walnuts contain higher

level of phytosterols than English walnuts, 109 mg/100g to 72 mg/100g of nut (USDA/ARS,

2008). In the intestinal lumen, phytosterols can promote reduction of cholesterol absorption,

thus lowering plasma cholesterol levels. The mechanism of action of phytosterols has been

associated to their high affinity for micelles than cholesterol. Consequently, cholesterol is

displaced from micelles and the amount available for absorption is reduced (Ostlund, 2002;

Brauner et al., 2012). In all probability the phytosterol content of Black walnuts may

contribute to their cholesterol-lowering effect.

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Fig 1. Examples of phenolic acids, condensed tannins and flavonoids structure (adapted from

Pandey and Rizvi, 2009; Tsao, 2010).

3. Black walnuts potential to health outcomes

Although the compositional analysis of Black walnuts has revealed potentially health

promoting constituents, research remains limited on the effects of this type of nut on the

human health. In order to assess the potential health benefits of Black walnuts comparisons

with English walnut was conducted in this review, as several studies have linked the

consumption of these tree nuts with multible health impacts..

3.1 Black Walnuts versus Cardiovasculares Diseases

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Decades ofEepidemiological research have shown a strong correlation between nut

consumption and reduced risks of heart diseases. Four seminal studies conducted in U.S.

showing the relationship between several foods (including nuts) and chronic diseases are

presented; The Adventist Health Study, The Iowa Women’s Health Study, The Nurses’s

Health Study and The Physicians’ Health Study.

In the Adventist Health Study (Fraser et al., 1992), 27,000 California Seventh-day

Adventists provided information on their dietary and lifestyle habits during six years

whilecoronary heart disease (CHD) data was also obtained. Among the enquired foods, nut

consumption presented the greatest inverse relationship with the risk of non-fatal myocardial

infarction (MI) or death from CHD. Individuals who ate nuts five or more times per week

presented with 48% less risk of MI and 38% less risk of death from CHD compared to the

individuals who consumed nut less than once per week.

The consumption of 127 foods, including nuts, was correlated with the risk of CHD in

The Iowa Women’s Health Study (Kushi et al., 1996). Similar to the previous study, a food

frequency questionnaire was applied and lifestyle habits were also. After 7 years of follow-

up, data from 19,411 women who were not taking vitamin supplements showed a 40%

reduction of fatal CHD risk in the group with highest nut consumption (more than 4 times per

month) compared to the group with the lowest consumption (rarely or never).

The results from The Nurses’s Health Study (Hu et al. 1998) also reported a cardio-

protective effect of nuts consumption. During 14 years, data from 86,016 nurses were

collected and analyzed regarding to the intake of 61 foods, including nuts, lifestyle and

occurrence of CHD. In the group with high intake of nuts (≥5 times per week), the risk of

fatal and non-fatal MI decreased by 39% and 32%, respectively, compared to the group

eating nuts less than once per month. The Physicians’ Health Study showed comparable with

the previous works, but it had less impact. Male physicians totaling 22,017 participated of

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this study during 17 years of follow up. The group who consumed nuts more than once per

week presented with 20% less risk of sudden cardiac death, however no reduction was

detected for non-fatal MI, which was attributed to the low frequency of nut consumption in

this studied population (Albert et al., 2002).

Consistent with those prospective studies, Estruch et al. (2013) published a recent

study that included 7447 subjects (57% women) with a high cardiovascular risk were

randomized to one of three diets, a Mediterranean diet supplemented with extra-virgin olive

oil, a Mediterranean diet supplemented with mixed nuts (50% of walnuts), or a control diet,

during 4.8 years. In summary, the results showed that the experimental diets led to a

reduction of the major cardiovascular events (myocardial infarction, stroke, or death from

CHD).

The cardiovascular effects of nuts consumption can be mainly attributed to their rich

content of omega-3 PUFAs and antioxidants, as several epidemiologic studies have

demonstrated significant associations between the intake of those nutrients and a reduced risk

of CVDs (Banel and Hu, 2009; Scalbert et al, 2005; Vanschoonbeek et al., 2003). Omega-3

fatty acids are related to improvements in plasma lipids and endothelial function (West et al.

2005; Steer et al., 2003). English walnuts contain the highest amount of α-linolenic acid

among all edible plants and their antioxidant polyphenols content is noteworthy (Crews et al.,

2005; Fukuda et al, 2003). Accordingly, several studies have been performed with the

purpose of investigating the cardio-protective effect of English walnuts.

West et al. (2010) assessed the effects of ALA on the vascular endothelial function in

20 hypercholesterolemic subjects using a randomized crossover study. Individuals were fed

an average American diet, which contained 8.7% energy from PUFA (7.7% LA, 0.8% ALA),

LA diet containing PUFA from whole walnuts and walnut oil that provided 16.4% of energy

(12.6% LA, 3.6% ALA) and ALA diet containing 17% energy from PUFA from walnuts,

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walnut oil, and flax oil (10.5% LA, 6.5% ALA). It was reported that experimental diets

(ALA and LA) significantly reduced diastolic blood pressure (-2 to -3 mm Hg) and total

peripheral resistance (-4%). Flow-mediated dilation and arginine-vasopressin were increased

after intake of the ALA diet. Data from this study suggest novel mechanisms for the cardio-

protective effects of English walnuts.

Nergiz-Ünal et al. (2013) demonstrated that the intake of English walnut influenced

plasma lipids levels and atherosclerotic plaque formation through an intervention study using

mice as animal model. Proatherogenic Apoe(-/-) mice were fed during eight weeks with a

high fat diet supplemented with walnuts (rich in omega-3 PUFA and antioxidants), walnut oil

(with omega-3 PUFA only) or sunflower oil (control group). The consumption of whole

walnuts, but not walnut oil, led to a 55% reduction in atherosclerotic plaque formation in the

aortic arch compared to the control group. In addition, triglycerides, cholesterol and

prothrombin serum levels decreased in the first group by 36%, 23% and 21%, respectively.

Moreover, increased plasma antioxidant capacity was detected. The atheroprotective effect of

walnuts were attributed to the combination of n-3 PUFA with other antioxidants

components, likely polyphenols.

In a crossover study, the effects on serum lipids and other markers of CVDs risk were

evaluated in 18 hypercholesterolemic patients (9 women and 9 men) randomized into

sequences of diets containing 40% fat from English walnuts, virgin olive oil or almonds,

during 4 weeks each (Damasceno et al., 2011). The results showed that LDL-cholesterol

(LDL-c) was significantly decreased by 7.3%, 10.8% and 13.4% after the olive oil, English

walnut and almond diets, respectively, when compared to baseline. Similarly, total

cholesterol and LDL/HDL ratios were significantly reduced, but only after nut diets. This

study is consistent with those reporting the well-established cholesterol lowering properties of

nut consumption.

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Also performing a randomized crossover study, Torabian et al. (2010) investigated a

long duration consumption of English walnuts by 87 individuals (38 men and 49 women)

with normal to moderate high plasma total cholesterol. The participants were assigned = a

walnut-supplemented diet (approximately 12% of total daily energy intake) or habitual diet

(control group) for six months each. The results showed that walnuts supplementation

decreased total cholesterol and triglyceride levels, which was more significant in the high

plasma total cholesterol group (at baseline). They also detected a high degree of dietary

compliance (95%), indicating that people can maintain a walnut-rich diet for long periods.

Those effects of English walnuts on lipid profile were consistent with the previous

commented studies and others (Banel and Hu, 2009; Almario et al., 2001, Olmedilla-Alonso

et al., 2008).

Despite the potentially health-promoting content, studies involving Black walnuts and

their effect on CVDs or other disease states are limited. Fitschen (2010) investigated the

cardiovascular effect of Black versus English walnuts consumption during 28-30 days. 29

participants (13 men and 16 women) were randomly selected to Black or English walnuts

consumption and after a 12-week washout period they switched to the other type of walnut

and consumed 30 g daily for more 28-30 days. The results showed that the walnuts intake led

to a 2.7% reduction of total cholesterol and 4.2% of LDL-cholesterol. Importantly, the author

reported that Black walnut consumption resulted in significantly improvement of the blood

lipids than English walnuts. In another study, Rorabaugh et al. (2011) compared the

antioxidant activity of English versus Black walnuts, through the ability to prevent oxidation

of LDL-c, which was assessed in-vitro using walnuts extracts and ex-vivo after walnuts intake

during 28 days by 36 subjects randomized to consume their habitual diets supplemented with

either with 30 g of English or Black walnuts. The results revealed that both walnuts improved

markers of oxidation, with English walnuts exhibiting a higher antioxidant capacity via an in-

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vitro assay. However, the consumption of walnuts (30g daily/28days) was not sufficient to

improve protection of LDL oxidation.

Based on these few studies and considering that Black walnuts are rich in many

bioactive compounds that are present in English walnuts, such as PUFAs, polyphenols,

vitamin E, fiber and arginine, ]] (Dreher and Maher, 1996; Huynh and Chin-Dusting, 2006),

Black walnuts consumption also could provide protective benefits against CVDs. However,

more research using black walnuts is needed to determine its cardiovascular health promoting

properties.

3.1 Black Walnuts versus Cancer

Epidemiological studies have shown a significant association between regular

consumption of fruits, nuts and vegetables, and a lower incidence of certain types of cancer

(Reddy et al., 2003; Mathew et al., 2004; Gonzales et al 2006). Some bioactive compounds

presnet nuts are reported to poccess potent antioxidant, anti-inflammatory or

chemopreventive properties, including omega-3 fatty acids (Berquin et al., 2008), tocopherol

(vitamin E), phytosterols, folate and polyphenols (Segura et al. 2006, Gonzales et al 2006).

Importantly, Black and English walnuts are excellent sources of these components (Table 1).

Moreover, walnuts contain the highest content of antioxidants, mainly polyphenolic

compounds and tocopherols (Blomhoff et al., 2006) compared to other nuts.

Carvalho et al. (2010) investigated the antiproliferative and antioxidant activities of

English walnut in human renal cancer cell lines A-498 and 769-P and the colon cancer cell

line Caco-2. The results showed that walnuts extract were able to inhibit the growth of those

cells in a dose-dependent manner. This inhibition was not correlated with the total phenolic

contents in the extracts tested, suggesting that a specific or a class of phytochemical in

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extracts may be responsible for their antiproliferative activities. In addition, after induced

oxidative hemolysis of human erythrocytes the walnut extracts significantly protected their

membrane from hemolysis in a time- and concentration-dependent manner. Data from this

work suggest that walnuts are an excellent source of antioxidantatvie and anti-cancer agents.

Polyphenols may act as anti-cancer agents through the following mechanisms: (a)

suppression the activation of nuclear factor-kB (NF-kB), which regulates the expression of

genes involved in inflammation and carcinogenesis; (b) inhibition of the activator protein-1

(AP-1) transcription factor, which has increased function by carcinogenesis-promoting agents;

(c) suppression of mitogen activated protein kinases (MAPK); (d) suppression of the protein

kinases PKC; (e) suppression of growth-factor receptor (GFR)-mediated pathways; (f) cell

cycle arrest and induction of apoptosis; (g) antioxidant and anti-inflammatory effects; and (h)

suppression of angiogenesis (Bonfili et al., 2008; Fresco et al.,2006).

In a study using mice as animal models, Nagel et al. (2012) demonstrated that dietary

walnuts inhibited colorectal cancer by suppressing angiogenesis. HT-29 human colon cancer

cells were injected in female mice, which were thenrandomized to diets containing

approximately 19% of total energy from English walnuts, flaxseed oil, or corn oil (control

group) for 25 days. Walnut and flaxseed diets were responsible for slowing tumor

development compared to the control group by 27% and 43%, respectively, while tumor

weight was also reduced. In addition, plasma expression levels of angiogenesis factors were

significantly reduced in mice fed on experimental diets. Angiogenesis was significantly

decreased only in walnut diet compared to the control. The authors suggest that more studies

should be performed in order to verify if walnuts supplementation have similar effects on

colon cancer in humans.

As previously exposed, Black walnuts contains a sizeable content of γ-tocopherol

(Table 1), a nutrient linked to protection against risks for prostate cancer (Chan et al., 1998;

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Helzlsouer et al., 2000). For example, γ-tocopherol inhibited tumor cells growth for a variety

of cancer cells including prostate cancer cells (Gysin et al., 2002). In a clinical study,

Spaccarotella et al. (2008), aimed to evaluate the effects of English walnuts supplementation

on markers of prostate cancer. Twenty one men at risk for prostate cancer were randomized

into their usual diet with or without 75 g of walnuts during eight weeks. Walnuts

supplementation led to an increased plasma γ-tocopherol and increased ratio of free prostate

specific antigen (PSA): total PSA compared to the control diet. In this study, the results

confirmed the potential anti-cancer effect of γ-tocopherol present in English walnuts.

Thus, Black walnuts have a promising potential on cancer prevention as it has similar

chemopreventive agents to English walnuts, especially polyphenolic compounds and γ-

tocopherol vitamin E, which are present even in higher amounts in the black walnuts (Table

1).

3.2 Black walnuts versus Diabetes and Neurodegenerative Diseases

Recent evidence suggests that the type of lipids is more important for type 2 diabetes

development than the total intake of fat (Risérus et al., 2009). Studies have reported a

relationship between the higher intake of MUFAs and PUFAs and lower intake of saturated

fat and trans-fat with a decrease in the risk of type-2 diabetes (Risérus et al., 2009). Thus, nut

consumption may play an important role on type-2 diabetes as the saturated fatty acid content

of this food is low (4-16%) and the unsaturated fatty acids levels are high (Ros and Mataix,

2006). As showed in Table 1, Black and English walnuts composition alighn t with this

information. Compared to English walnuts, Black walnuts contain less saturated fat and more

MUFAs content; although the PUFAs profile is lower in Black walnuts, it is still higher than

in the other commercial edible nuts (Ros, 2010). Walnuts also contain several other bioactive

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components that may be associated with the beneficial effects on type-2 diabetes, such

dietary fiber, sterols, vegetable protein, and antioxidants (Pan et al., 2013).

Pan et al. (2013) assessed the relationship between English walnut consumption and

the prevalence of type-2 diabetes in two seminal studies, the Nurses’ Health Study (NHS) 1

and 2. Women (58,063 aged 52–77 years and 79,893 aged 35–52 years) without diabetes,

cardiovascular disease, or cancer at baseline, participated in NHS 1 and NHS 2, respectively,

during 10 years of follow-up. Consumption of walnuts and other edible nuts was investigated

every 4 years by applying food frequency questionnaires. After multivariate adjustment for

traditional risk factors, walnut consumption was associated with a lower risk of type 2

diabetes, which persisted after adjustment for other lifestyle factors. This study indicates that

frequent ingestion of walnuts may be responsible for reducing risk of type-2 diabetes in

women. However, further studies are needed in order to confirm their protective role..

The benefial effects promoted by walnuts intake also extends to brain health. Recent

studies have demonstrated that animals fed diets rich in walnuts presented with improved

indices of memory, cognition and motor functions (Joseph et al., 2005; Joseph et al., 2009;

Willis et al., 2009c). α-linolenic acid rich foods are associated with brain health , namely

EPA and DHA, play a crucial role in brain health by maintaining synaptic plasticity,

neuronal membrane stability, gene expression, mitigation of oxidative stress and regulation of

immune function (Willis et al., 2009a and 2009b). In addition, other nutrients, such as

vitamin E, folate, phenolic compounds, melatonin and other micronutrients, have also been

related to neuroprotective effects (Willis et al., 2009b and 2009c).

Poulose et al. (2012) investigated whether English walnut diet could activate

autophagy function to maintain protein homeostasis, thus preventing the accumulation of

polyubiquitinated proteins in brain of aged rats. The accumulation of these toxic proteins in

brain increases with age, in part due to increased oxidative and inflammatory stresses and is a

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biomarker of several neurodegenerative diseases. After consuming a 6% or 9% walnut diet,

19-month-old rats presented with significantly reduced aggregation of polyubiquitinated

proteins. Also, those animals exhibited up-regulation of autophagy. The Theresults revealed

that a walnut-rich diet is effective on activation of the autophagy function in brain and also

antioxidant and anti-inflammatory benefits were demonstrated.

In an in-vitro study, Willis et al. (2010) examined the effects of English walnut extract

on LPS-induced activation in BV-2 microglial cells. Microglial activation can result in the

production of cytotoxic intermediates, being correlated with a variety of age-related and

neurodegenerative diseases. The ensuing data showed that cells treated with walnut extract

produced lower amounts of nitric oxide and reduced expression of inducible nitric oxide

synthase. Walnut supplementation also induced a reduction in tumor necrosis-alpha (TNF-α)

generation and internalization of the LPS receptor toll-like receptor 4. This first study

showing the anti-inflammatory effects of walnuts in microglia indicates that this edible nut

may play an important role in the prevention/treatment of neurodegenerative conditions and

the most likely nutrients involved in this function would be essential fatty acids.

The similar fatty acids composition of Black walnuts compared to English walnuts

and also the presence of other bioactive agents suggests that the Black walnuts may also

positively affect diabetes and neurodegenerative conditions through the same mechanisms

cited above. However, future research using this particular type of edible walnut needs to be

accomplished to consolidate these estimated results.

4. Conclusion

Black walnuts are the second most produced walnut in U.S., but their commercial

value is not as high as for English walnuts because of the difficulty in processing of their

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seeds. However, the nutritional composition of Black walnut shows that this edible nut is a

rich source of bioactive compounds capable of promoting multiple health benefits. The

purpose of this review was to estimate the health-promoting potential through the

consumption of Black walnuts based on data obtained from English walnuts research, as such

studies with Black walnuts are almost inexistent. For example, Black walnuts contain high

levels of polyunsaturated fatty acids (i.e. α-linolenic acid) and antioxidant compounds, as

polyphenols and γ-tocopherol. These compounds have been associated with English walnuts

consumption in terms of their protection against multiple diseases, including cardiovascular

health, certain cancers, diabetes, neurodegenerative conditions, and others disease states

related to oxidative and inflammatory stress. In addition, others agent present in Black

walnuts have been linked to health promoting, including dietary fiber, folate, phytosterols,

arginine, melatonin, among others. In summary, data showing health benefits through the

English walnuts intake supports the characterization of Black walnuts as effective functional

foods. However, future research using specifically Black walnut is needed in order to

understand it function in human body and promote its inclusion in the diet.

References

Agricultural Marketing Resource Center (AgMRC). 2007. Growing Black Walnut for Nut

Production. Available online:

Page 20: Black Walnuts (Juglans nigra L.): Potential as a Health ...Walnuts, almonds and pecans are the top three nuts consumed in the United States (USDA/ERS, 2012a). Walnut is the second

20

http://www.agmrc.org/media/cms/walnutNuts_A6DC9E4D376F7.pdf (accessed on 19

February 2013).

Albert MC, Gaziano M, Willet, WC, Manson JE. Nut consumption and drecreased risk of

sudden cardiac death in the Physicians’ Health Study. Arch Intern Med 2002;162:1382-1387.

Almario RU, Veraphon Vonghavaravat, Rodney Wong, and Sidika E Kasim-Karakas. Effects

of walnut consumption on plasma fatty acids and lipoproteins in combined hyperlipidemia.

Am J Clin Nutr 2001;74:72–9.

Anderson KJ, Teuber SS, Gobeille A, Cremin P,Waterhouse AL, Steinberg FM.Walnut

polyphenolics inhibit in vitro human plasma and LDL oxidation. J Nutr 2001;131:2837–42.

Banel DK, Hu FB. Effects of walnut consumption on blood lipids and other cardiovascular

risk factors: a meta-analysis and systematic review. Am J Clin Nutr 2009;90:56–63.

Berquin, I.M., Edwards, I.J., Chen, Y.Q., 2008. Multi-targeted therapy of cancer by omega-3

fatty acids. Cancer Lett. 269, 363–377.

Blomhoff, R., Carlsen, M., Andersen, L., Jacobs Jr., D., 2006. Health benefits of nuts:

potential role of antioxidants. Br. J. Nutr. 96, S52–S60.

Bonfili, L., Cecarini, V., Amici, M., Cuccioloni, M., Angeletti, M., Keller, J.N., Eleuteri,

A.M., 2008. Natural polyphenols as proteasome modulators and their role as

anticancer compounds. FEBS J. 275, 5512–5526.

Brauner R, Johannes C, Ploessl F, Bracher F, Lorenz RL. Phytosterols reduce cholesterol

absorption by inhibition of 27-hydroxycholesterol generation, liver X receptor α activation,

and expression of the basolateral sterol exporter ATP-binding cassette A1 in Caco-2

enterocytes. J Nutr. 2012 Jun;142(6):981-9.

Brufau, G.; Boatella, J.; Rafecas, M. Nuts, source of energy and macronutrients. Br. J. Nutr.

2006, 96, S24-S28.

Canales A, Benedi J, Nus M, Librelotto J, Sanchez-Montero JM, Sanchez-Muniz FJ.

Effect of walnut-enriched restructured meat in the antioxidant status of overweight/obese

senior subjects with at least one extra CHD-risk factor. J Am Coll Nutr 2007;26:225–32.

Carvalho, M., Pedro J. Ferreira a, Vanda S. Mendes b, Renata Silva b, José A. Pereira c,

Page 21: Black Walnuts (Juglans nigra L.): Potential as a Health ...Walnuts, almonds and pecans are the top three nuts consumed in the United States (USDA/ERS, 2012a). Walnut is the second

21

Carmen Jerónimo d,e, Branca M. Silva. Human cancer cell antiproliferative and antioxidant

activities of Juglans regia L. Food and Chemical Toxicology 48 (2010) 441–447

Chan J, Stampfer M, Giovannucci E, Gann P, Ma J, Wilkinson P, Hennekens C, Pollak M:

Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science

1998,

279:563-566.

Crews C, Hough P, Godward J, et al. (2005) Study of main constituents of some authentic

walnut oils. J Agric Food Chem 53, 4853–4860.

Damasceno, N. R. T., A. Pe´rez-Heras a,c, M. Serra a,c, M. Cofa´n a,c, A. Sala-Vila a,c, J.

Salas-Salvado´ c,d, E. Ros. Crossover study of diets enriched with virgin olive oil, walnuts or

almonds. Effects on lipids and other cardiovascular risk markers. Nutrition, Metabolism &

Cardiovascular Diseases (2011) 21, S14eS20.

Das UN. Essential fatty acids – a review. Curr Pharm Biotechnol 2006;7:467–82.

Djoussé, L.; Rudich, T.; Gaziano, J.M. Nut consumption and risk of heart failure in the

Physicians’ Health Study I. Am. J. Clin. Nutr. 2008, 88, 930-933.

Dreher ML, Maher CV. The traditional and emerging role of nuts in healthful diets. Nutr Rev

1996;54:241­5.

Estruch R, Emilio Ros, M.D., Ph.D., Jordi Salas-Salvadó, M.D., Ph.D., Maria-Isabel Covas,

D.Pharm., Ph.D., Dolores Corella, D.Pharm., Ph.D., Fernando Arós et al. Primary Prevention

of Cardiovascular Disease with a Mediterranean Diet. N Engl J Med 2013;368(14):1279-

1290.

Fitschen, P. Cardiovascular effects of black versus English walnut consumption. University

of Wisconsin-La Crosse. 2010

Fraser GE, Sabate J, Beeson WL, Strahan TM. A possible protective effect of nut

consumption on risk of coronary heart disease. The Adventist Health Study. Arch Intern Med

1992;152:1416­24.

Fresco, P., Borges, F., Diniz, C., Marques, M.P., 2006. New insights on the anticancer

properties of dietary polyphenols. Med. Res. Rev. 26, 747–766.

Page 22: Black Walnuts (Juglans nigra L.): Potential as a Health ...Walnuts, almonds and pecans are the top three nuts consumed in the United States (USDA/ERS, 2012a). Walnut is the second

22

Fukuda, T., Ito, H., & Yoshida, T. (2003). Antioxidative polyphenols from walnut (Juglans

regia L.). Phytochemistry, 63, 795–801.

Gysin R, Azzi A, Visarius T: Gamma-tocopherol inhibits human cancer cell cycle

progression and cell proliferation by down regulation of cyclins. FASEB J 2002, 16:1952-

1954.

Gonzalez, C.A.; Salas-Salvadó, J. The potential of nuts in the prevention of cancer. Br. J.

Nutr.

2006, 96, S87-S94.

Harris, W.S.; Miller, M.; Tighe, A.P.; Davidson, M.H.; Schaefer, E.J. Omega-3 fatty acids

and coronary heart disease risk: Clinical and mechanistic perspectives. Atherosclerosis 2008,

197,12–24.

Helzlsouer K, Huang H, Alberg A, Hoffman S, Burke A, Norkus E, Morris J, Comstock G:

Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate

cancer. J Natl Cancer Inst 2000, 92:2018-2023.

Hu, F.B., Meir J Stampfer, JoAnn E Manson, Eric B Rimm, Graham A Colditz, Bernard A

Rosner, Frank E Speizer, Charles H Hennekens,Walter C Willett. Frequent nut consumption

and risk of coronary heart disease in women: prospective cohort study. BMJ 1998;317:1341–

5

Huynh, N.N.; Chin-Dusting, J. Amino acids, arginase and nitric oxide in vascular health.

Clin.Exp. Pharmacol. Physiol. 2006, 33, 1-8.

Ito, H., Okuda, T., Fukuda, T., Hatano, T., & Yoshida, T. (2007). Two novel dicarboxylic

acid derivatives and new dimeric hydrolysable tannin from walnuts. Journal of

Agricultural and Food Chemistry, 55, 672–679.

Joseph JA, Shukitt-Hale B, Willis LM. Grape juice, berries, and walnuts affect brain

aging and behavior. J Nutr 2009;139:1813S–7S.

Joseph JA, Shukitt-Hale B, Casadesus G. Reversing the deleterious effects of aging on

neuronal communication and behavior: beneficial properties of fruit polyphenolic

compounds. Am J Clin Nutr 2005;81:313S–6S.

Page 23: Black Walnuts (Juglans nigra L.): Potential as a Health ...Walnuts, almonds and pecans are the top three nuts consumed in the United States (USDA/ERS, 2012a). Walnut is the second

23

Labuckas, D O, Damián M. Maestri, Milton Perelló, Marcela L. Martínez, Alicia L.

Lamarque. Phenolics from walnut (Juglans regia L.) kernels: Antioxidant activity and

interactions with proteins.Food Chemistry 2008, 107 (2), 607-612.

Karamac, M. (2009). In-vitro study on the efficacy oftannin fractions of edible nuts as

antioxidants. Eur J Lipid Sci Technol. 111:1063-1071

Khanbabaee, K., Ree, T. van. Tannins: Classification and Definition. Nat. Prod. Rep., 2001,

18, 641–649.

Kris-Etherton, P.M. Omega-3 fatty acids and cardiovascular disease: New recommendations

from the American heart association. Arterioscler. Thromb. Vasc. Biol. 2003, 23, 151–152.

Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y & Bostick RM (1996) Dietary

antioxidant vitamins and death from coronary heart disease in postmenopausal women. N

Engl J Med 334, 1156–1162.

Leaf, A.; Kang, J.X.; Xiao, Y.-F. Fish oil fatty acids as cardiovascular drugs. Curr. Vasc.

Pharmacol. 2008, 6, 1–12.

Ma Y, Njike VY, Millet J, Dutta S, Doughty K, Treu JA, et al. Effects of walnut consumption

on endothelial function in type 2 diabetic subjects: a randomized controlled crossover trial.

Diabetes Care 2010;33:227–32.

Manach C, Williamson G, Morand C, Scalbert A, Remesy C. Bioavailability and bioefficacy

of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr

2005;81:230S–42S.

Mathew, A., Peters, U., Chatterjee, N., Kulldorff, M., Sinha, R., 2004. Fat, fiber, fruits,

vegetables, and risk of colorectal adenomas. Int. J. Cancer 108, 287–292.

McKay DL, Chen CY, Yeum KJ, Matthan NR, Lichtenstein AH, Blumberg JB. Chronic

and acute effects of walnuts on antioxidant capacity and nutritional status in

humans: a randomized, cross-over pilot study. Nutr J 2010;9:21.

Nagel JM, Mary Brinkoetter M.S. a, Faidon Magkos Ph.D. a, Xiaowen Liu Ph.D. a, John P.

Chamberland B.Sc. a, Sunali Shah B.Sc. Dietary walnuts inhibit colorectal cancer growth in

mice by suppressing angiogenesis. Nutrition 28 (2012) 67–75

Nergiz-Ünal R, Marijke J.E. Kuijpers, Susanne M. de Witt, Sylvia Heeneman, Marion A.H.

Feijge, Sonia C. Garcia Caraballo et al. Atheroprotective effect of dietary walnut intake in

Page 24: Black Walnuts (Juglans nigra L.): Potential as a Health ...Walnuts, almonds and pecans are the top three nuts consumed in the United States (USDA/ERS, 2012a). Walnut is the second

24

ApoE-deficient mice:Involvement of lipids and coagulation factors. Thrombosis Research

xxx (2013) xxx–xxx

Oliveira I, Sousa A, Ferreira IC, Bento A, Estevinho L, Pereira JA. Total phenols, antioxidant

potential and antimicrobial activity of walnut (Juglans regia L.) green husks. Food Chem

Toxicol 2008;46:2326–31.

Olmedilla-Alonso B, F. Granado-Lorencio, PhD, C. Herrero-Barbudo, MBiol, I. Blanco-

Navarro, S. Bla´zquez-Garcı´a, MChem, B. Pe´rez-Sacrista´n. Consumption of Restructured

Meat Products with Added Walnuts Has a Cholesterol-Lowering Effect in Subjects at High

Cardiovascular Risk: A Randomised, Crossover, Placebo-Controlled Study. Journal of the

American College of Nutrition, Vol. 27, No. 2, 342–348 (2008).

Ostlund RE Jr. Phytosterols in human nutrition. Annu Rev Nutr. 2002;22:533–49.

Pan, A.; Qi Sun,3,6 JoAnn E. Manson,3,4,7 Walter C. Willett,3,4,6 and Frank B. Hu. Walnut

Consumption Is Associated with Lower Risk of Type 2 Diabetes in Women. The Journal of

Nutrition, Nutritional Epidemiology. J. Nutr. 2013; 143: 512–518

Pandey, K.B.; Rizvi, S.I. Plant polyphenols as dietary antioxidants in human health and

disease.Oxid. Med. Cell. Longev. 2009, 2, 270–278.

Pereira JA, Oliveira I, Sousa A, Valentao P, Andrade PB, Ferreira IC, et al. Walnut (Juglans

regia L.) leaves: phenolic compounds, antibacterial activity and antioxidant potential of

different cultivars. Food Chem Toxicol 2007;45:2287–95.

Poulose, S. M.; Donna F. Bielinski, Barbara Shukitt-Hale. Walnut diet reduces accumulation

of polyubiquitinated proteins and inflammation in the brain of aged rats. Journal of

Nutritional Biochemistry xx (2012) xxx–xxx

Reddy, L., Odhav, B., Bhoola, K.D., 2003. Natural products for cancer prevention: a

global perspective. Pharmacol. Ther. 99, 1–13.

Risérus U, Willett WC, Hu FB. Dietary fats and prevention of type 2 diabetes. Prog Lipid

Res. 2009;48:44–51.

Rorabaugh, J M, Ajay P. Singh, Isabel M. Sherrell, Michelle R. Freeman, Nicholi Vorsa,

Peter Fitschen, Christopher Malone, Margaret A. Maher, Ted Wilson. English and Black

Walnut Phenolic Antioxidant Activity in Vitro and Following Human Nut Consumption.

Food and Nutrition Sciences, 2011, 2, 193-200.

Page 25: Black Walnuts (Juglans nigra L.): Potential as a Health ...Walnuts, almonds and pecans are the top three nuts consumed in the United States (USDA/ERS, 2012a). Walnut is the second

25

Ros, E.; Mataix, J. Fatty acid composition of nuts. Implications for cardiovascular health. Br.

J.Nutr. 2006, 96, S29-S35.

Ros, E. Health Benefits of Nut Consumption. Nutrients 2010, 2, 652-682.

Scalbert A , Claudine Manach , Christine Morand , Christian Rémésy & Liliana Jiménez

(2005): Dietary Polyphenols and the Prevention of Diseases, Critical Reviews in Food

Science and Nutrition, 45:4, 287-306

Segura, R.; Javierre, C.; Lizarraga, M.A.; Ros, E. Other relevant components of nuts,

phytosterols, folate and minerals. Br. J. Nutr. 2006, 96, S36-S44.

Simopoulos, A.P. Essential fatty acids in health and chronic disease. Am. J. Clin. Nutr. 1999,

70,560S–569S.

Spaccarotella KJ, Penny M Kris-Etherton2, William L Stone3,Deborah M Bagshaw2, Valerie

K Fishell2, Sheila G West. The effect of walnut intake on factors related to prostate and

vascular health in older men. Nutrition Journal 2008, 7:13

Steer P, Vessby B, Lind L: Endothelial vasodilatory function is related to the proportions of

saturated fatty acids and alphalinolenic acid in young men, but not in women. Eur J Clin

Invest 33:390–396, 2003.

Tapsell LC, Gillen LJ, Patch CS, Batterham M, Owen A, Bare M, et al. Including walnuts in

a low-fat/modified-fat diet improves HDL cholesterol-to-total cholesterol ratios in patients

with type 2 diabetes. Diabetes Care 2004;27:2777–83.

Torabian S, E Haddad, Z Cordero-MacIntyre, J Tanzman, ML Fernandez3and J Sabate.

Long-term walnut supplementation without dietary advice induces favorable serum lipid

changes in free-living individuals. European Journal of Clinical Nutrition 2010; 64: 274–279.

Tsao, R. Chemistry and biochemistry of dietary polyphenols. Nutrients 2010, 2, 1231–1246.

U.S. Department of Agriculture, Economic Research Service. 2005. Fruit and Tree Nut

Outlook. Available online: http://usda01.library.cornell.edu/usda/ers/FTS//2000s/2005/FTS-

09-28-2005.pdf (accessed on 18 March 2013).

U.S. Department of Agriculture, Economic Research Service. 2012a. Fruit & Tree Nuts.

Available online: http://www.ers.usda.gov/topics/crops/fruit-tree-

nuts/background.aspx#treenuts (accessed on 16 March 2013).

Page 26: Black Walnuts (Juglans nigra L.): Potential as a Health ...Walnuts, almonds and pecans are the top three nuts consumed in the United States (USDA/ERS, 2012a). Walnut is the second

26

U.S. Department of Agriculture, Economic Research Service. 2012b. Fruit and Tree Nut

Yearbook. Table F17 (Walnuts). Available online:

http://usda.mannlib.cornell.edu/MannUsda/viewDocumentInfo.do?documentID=1377

(accessed on 16 March 2013).

U.S. Department of Agriculture, Economic Research Service. 2012c. Fruit and Tree Nut

Yearbook. Table F7 (Almonds). Available online:

http://usda.mannlib.cornell.edu/MannUsda/viewDocumentInfo.do?documentID=1377

(accessed on 16 March 2013).

U.S. Department of Agriculture, Agricultural Research Service. 2012. USDA National

Nutrient Database for Standard Reference, Release 25. Nutrient Data Laboratory Home Page,

http://www.ars.usda.gov/ba/bhnrc/ndl

U.S. Department of Agriculture, Agricultural Research Service. 2008. USDA National

Nutrient Database for Standard Reference, Release 21. Nutrient Data Laboratory Home Page,

http://www.ars.usda.gov/ba/bhnrc/ndl

Vanschoonbeek K, de Maat MP, Heemskerk JW. Fish oil consumption and reduction of

arterial disease. J Nutr. 2003 Mar;133(3):657-60.

Wagner, K.H.; Kamal-Eldin, A.; Elmadfa, I.U. Gamma-tocopherol - An underestimated

vitamin?

Ann. Nutr. Metab. 2004, 48, 169-188.

Welch, G.N.; Loscalzo, J. Homocysteine and atherothrombosis. N. Engl. J. Med. 1998, 338,

1042-1050.

West SG, Hecker KD, Mustad VA, Nicholson S, Schoemer SL, Wagner P, Hinderliter AL,

Ulbrecht J, Ruey P, Kris-Etherton PM: Acute effects of monounsaturated fatty acids with and

without omega-3 fatty acids on vascular reactivity in individuals with type 2 diabetes.

Diabetologia 48:113–122, 2005.

West, SG, Andrea Likos Krick, PhD, Laura Cousino Klein, PhD, Guixiang Zhao, PhD, Todd

F. Wojtowicz, JD,Matthew McGuiness et al. Effects of Diets High in Walnuts and Flax Oil

on Hemodynamic Responses to Stress and Vascular Endothelial Function. Journal of the

American College of Nutrition, 2010,Vol. 29, No. 6, 595–603.

Willis LM, Bielinski DF, Fisher DR, Matthan NR, Joseph JA. Walnut extract inhibits

Page 27: Black Walnuts (Juglans nigra L.): Potential as a Health ...Walnuts, almonds and pecans are the top three nuts consumed in the United States (USDA/ERS, 2012a). Walnut is the second

27

LPS-induced activation of BV-2 microglia via internalization of TLR4: possible involvement

of phospholipase D2. Inflammation 2010;33:325–33.

Willis LM, Shukitt-Hale B, Joseph JA. Dietary polyunsaturated fatty acids improve

cholinergic transmission in the aged brain. Genes Nutr 2009a;4:309–14.

Willis LM, Shukitt-Hale B, Joseph JA. Modulation of cognition and behavior in aged

animals: role for antioxidant- and essential fatty acid-rich plant foods. Am J Clin Nutr

2009b;89:1602S–6S.

Willis LM, Shukitt-Hale B, Cheng V, Joseph JA. Dose-dependent effects of walnuts

on motor and cognitive function in aged rats. Br J Nutr 2009c;101:1140–4.

Yang, J., Liu, R., Halim, L., 2009. Antioxidant and antiproliferative activities of

common edible nut seeds. Food Sci. Technol. 42, 1–8.